Process for preparing 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination of the corresponding acid in the presence of a tertiary amine salt or quaternary ammonium salt

Abstract

A process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorinating 5-amino-2,4,6-triiodoisophthalic acid with thionyl chloride in the presence of a suitable solvent and of a tertiary amine salt or quaternary ammonium salt in a molar ratio from 1;1 to 1;2 with respect to 5-amino-2,4,6-triiodoisophathalic acid is described. 5-amino-2,4,6-triiodoisophthalic acid dichloride is an intermediate useful for the preparation of iodinated contrast agents.

We claim: 
     
       1. A process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination of 5-amino-2,4,6-triiodoisophthalic acid with thionyl chloride in the presence of a solvent characterized in that the reaction is carried out in the presence of a tertiary amine salt or quaternary ammonium salt in a molar ratio from 1:1 to 1:2 with respect to 5-amino-2,4,6-triiodoisophthalic acid. 
     
     
       2. A process according to claim 1 wherein the amount of thionyl chloride is from 2 to 8 moles by mole of 5-amino-2,4,6-triiodoisophthalic acid. 
     
     
       3. A process according to claim 2 wherein the amount of thionyl chloride is from 4 to 6 moles by mole of 5-amino-2,4,6-triiodoisophthalic acid. 
     
     
       4. A process according to claim 1 wherein the tertiary amine salts or quaternary amine salts are tertiary amine hydrohalides or quaternary ammonium halides. 
     
     
       5. A process according to claim 4 wherein the salts are tertiary amine hydrochlorides or hydrobromides or quaternary ammonium chlorides or bromides. 
     
     
       6. A process according to claim 1 wherein the tertiary amines are trialkylamines. 
     
     
       7. A process according to claim 6 wherein the tertiary amine is triethylamine. 
     
     
       8. A process according to claim 1 wherein the quaternary ammonium salts are tetraalkylammonium salts. 
     
     
       9. A process according to claim 8 wherein the quaternary ammonium salt is selected among tetraethylammonium and tetrabutylammonium salts. 
     
     
       10. A process according to claim 1 wherein the tertiary amine salts or quaternary ammonium salts are selected among triethylamine hydrochloride, triethylamine hydrobromide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetraethylammonium bromide and tetraethylammonium chloride. 
     
     
       11. A process according to claim 10 wherein triethylamine hydrochloride is used. 
     
     
       12. A process according to claim 1 wherein the amount of tertiary amine salt or quaternary ammonium salt is equimolar with respect to 5-amino-2,4,6-triiodoisophthalic acid. 
     
     
       13. A process according to claim 1 wherein the solvent is selected among ethyl acetate, methylene chloride, chloroform and 1,2-dichloroethane. 
     
     
       14. A process according to claim 13 wherein the solvent is methylene chloride.